Acute effects of ethanol on steroidogenic acute regulatory protein (StAR) in the prepubertal rat ovary

Background: Steroidogenic acute regulatory protein (StAR) is a 30 kDa mitoc hondrial protein that plays an essential role in steroid hormone biosynthes is by facilitating delivery of cholesterol across the mitochondrial membran e, where side chain cleavage occurs to initiate ovarian steroidogenesis. Be cause ethanol (EtOH) suppresses estradiol secretion in prepubertal female r ats, we evaluated the effects of EtOH on prepubertal ovarian StAR. Methods: At 0700 hr. 28-day-old female rats were gavaged with saline or a 3 g/kg dose of EtOH. At 0800 hr, half of each of these two groups was treate d with 15 IU of pregnant mare serum gonadotropin (PMSG). At 1000 hr, a 2 g/ kg dose was administered to maintain moderately elevated blood alcohol leve ls. At 1600 hr, all of the animals were killed by decapitation, and blood a nd ovaries were collected for measurement of serum pregnenolone and estradi ol and for ovarian StAR gene and protein expression. Results: Northern blot analysis showed two major transcripts of 3.8 and 1.7 kb of ovarian StAR mRNA. The ovaries from EtOH-treated rats showed decreas ed (p<0.01) basal expression of both 3.8 and 1.7 kb StAR transcripts. PMSG- stimulated animals showed a more than 4-fold increase (p<0.001) in the leve ls of both transcripts, when compared with ovaries from animals that receiv ed saline or EtOH only. Conversely, in EtOH-treated animals, the PMSG-stimu lated expression of the 1.7 kb transcript was blocked, and the increase in the 3.8 kb StAR transcript was blunted (p<0.05 vs. PMSG). Western blot anal ysis revealed that EtOH exposure also depressed (p<0.01) the basal expressi on of StAR protein. PMSG-stimulated animals showed an increase (p<0.001) in levels of StAR protein, and this was blocked (p<0.01) by EtOH. These chang es observed in ovarian StAR mRNA and protein were paralleled by changes in serum pregnenolone and estradiol. Specifically, acute EtOH exposure suppres sed (p<0.05) the basal levels of both steroids. Furthermore, PMSG-stimulate d animals showed an increase in the production of pregnenolone (p<0.05) as well as estradiol (p<0.01), and EtOH blocked this stimulatory action of PMS G on both steroids. Conclusion: These results demonstrate for the first time that EtOH is capab le of altering ovarian StAR expression, which contributes to the detrimenta l effect this drug has on ovarian steroidogenesis during prepubertal develo pment.